The present invention relates generally to neurostimulators. More particularly, the invention describes a leadless ultrasound-based system configured for electrical stimulation of the brain.
Deep brain stimulation (DBS) is one of the most important therapies in modern functional neurosurgery. First approved by the FDA in 1997, deep brain stimulation inactivates, but does not destroy, the parts of the brain responsible for example for the movement disorders. Due to its safety profile and efficacy, DBS evolved from a last-resort therapeutic option to a modality that is now routinely offered to patients and has been used to treat various neurological disorders.
DBS of the thalamus is primarily used to treat disabling tremor, especially tremor that affects one side of the body substantially more than the other. Studies have shown that DBS may significantly reduce tremor in about two thirds of patients with Parkinson's disease (PD). Tremor may not be eliminated, and may continue to cause some impairment. DBS of the globus pallidus is useful in treatment of dyskinesias as well as tremor, and may improve other symptoms, as well. DBS of the subthalamic nucleus may have an effect on most of the main motor features of PD, including bradykinesia, tremor, and rigidity.
Treatment sites for movement disorders may be identified by probing brain tissue and a site predetermined for treatment is selected. As noted for movement disorders, known regions of the brain suitable for neurostimulation include, but are not limited to, the ventral intermediate thalamus, subthalamic nucleus, and internal globus pallidus.
Similarly, DBS has been pursued as a treatment for pain for the past 30 years. Peripheral pain signals are transmitted via the spinothalamic tract of the spinal cord and synapse primarily in the thalamus. Thus, the area where they synapse was seen as a prime target for DBS and was the focus of much of the early research. DBS continues to be pursued as a therapy in chronic pain patients. Today, the pain indications that either exist or seem most promising for potential treatment by deep brain stimulation include: neuropathic pain; Complex Regional Pain Syndrome (CRPS), Type II; steady, burning pain; lancinating, shooting pain; tactile hypersensitivity; or partial or complete sensory loss. The targets for DBS for pain typically include the following sites:
Neuropathic Pain: Medial Lemniscus, Ventrobasal (VB) area of the thalamus, including the ventral posteromedial (VPM) and the ventral posterolateral (VPL) nuclei, Internal Capsule, Motor Cortex, Cingulate gyrus (also known as cingulate cortex), Posterior complex of the thalamus (PO), Ventrolateral nucleus of the thalamus (VL).
Nociceptive Pain: Periventricular grey (PVG) matter and periaqueductal grey (PAG) matter, which are sometimes simply called periventricular grey and periaqueductal grey.
Similar targets in the brain are emerging for other DBS applications. Published targets for the treatment of depression would include, but are not limited to, one or more of the cerebellar vermis, the anterior cingulate gyrus, the dorsal prefrontal cortex, the dorsal raphe nuclei, the median raphe nuclei, and the locus coeruleus. Published targets for the treatment of epilepsy, obesity, and diabetes would include, but are not limited to, the nucleus of tractus solitarius (NTS), the sub thalamic nucleus, the hippocampus, the medial thalamus and the temporal lobe.
Upper regions of the brain, e.g., the cortex, that have been affected by stroke or injury also benefit from stimulation treatments and have been shown to be effective in rehabilitating motor performance of distal extremities. In this stroke rehabilitation treatment the electrode is placed on the dura, the membrane that covers the brain, and used to deliver stimulation to the cortex.
In addition to its established role for the treatment of movement disorders, promising results have now been reported in epilepsy and psychiatric diseases. New applications of DBS are currently being proposed for diseases previously considered out of the realm of neurosurgical therapies. DBS has now been suggested as an emergent treatment for various conditions, including depression, hypertension, Alzheimer's disease, Parkinson's disease, Tourette syndrome, obsessive compulsive disorder, minimally conscious states, memory improvement, aggressiveness, and even drug addiction and obesity. In recent years, in addition to its therapeutic effects, the use of DBS systems as part of brain-machine interfaces has been extensively discussed.
FIG. 1 illustrates conventional realization of DBS. Current DBS systems include one or more intracranial DBS electrodes 10 implanted into the subject's brain (typically in a thalamus section), optional adaptors to fix the electrodes in place, an implantable stimulator 40 such as an implantable pulse generator (IPG), and a lead 20 with an extension cable 30 to connect the DBS electrode 10 to the stimulator 40. About two weeks after implanting the electrode 10 and a lead 20, a separate surgery is performed to implant one or two neurostimulators 40 under the collarbone. Wires of the extension cable 30 are at the same time placed under the skin, which run behind the ears and down the neck, to connect the neurostimulators 40 with the leads 20. Surgery is required to replace the batteries of the neurostimulator 40 every three to six years, depending on use.
The leads 20 represent the least reliable part of the system shown in FIG. 1. Lead fracture is reported to be the most frequent failure of the system which typically necessitates a major surgery to correct the problem and replace the leads 20. There have been reported attempts to eliminate implant's leads, a major source of complications and reliability issue. There have been reported attempts to deal with the complications and limitations imposed by the use of electrical leads. For example, self-contained implantable microstimulators and remotely-powered microstimulators have been described; however, each approach suffers from some significant limitation. A self-contained microstimulator must incorporate a battery or some other power supply; this imposes constraints on size, device lifetime, available stimulation energy, or all three. Often, DBS devices contain rechargeable batteries due to high use or high energy requirements of the therapeutic stimulation. Implantation of the pulse generator into the skull has been proposed, which addresses the difficult procedural task of tunneling leads and avoids cosmetic appearance issues associated with the subcutaneous leads and pulse generators; however, the lead still must be placed into the brain and connected to the pulse generator.
As for remotely-powered devices, designs utilizing either radiofrequency (RF) or electromagnetic transformer power transmission have been proposed in the prior art. RF energy transmission, unless the transmitting and receiving antennae are placed in close proximity, suffers from inefficiency and restricted safe power transfer capabilities, limiting its usefulness in applications where stimulation must be accomplished at any significant depth (>1-2 cm) within the body, in particular where it is desired to permanently implant both the transmitter and receiver-stimulator. Electromagnetic coupling can more efficiently transfer electrical power, and can safely transfer higher levels of energy but again relies on close proximity between transmitting and receiving coils, or the utilization of relatively large devices for deeper implantation.
The following patents, all of which are incorporated in this disclosure in their entirety, describe various aspects of using electrical stimulation for achieving various beneficial effects. U.S. Pat. No. 5,716,377 titled “Method of Treating Movement Disorders by Brain Stimulation” by Rise et al. describes a typical implantable DBS system for treating movement disorders such as Parkinson's. U.S. Pat. No. 7,013,177 titled “Treatment of Pain by Brain Stimulation” by Whitehurst et al. describes an implantable DBS system that uses electrical stimulation in the form of a microstimulator in combination with drug delivery for the treatment of pain. U.S. Pat. No. 5,405,367 titled “Structure and Method of Manufacture of an Implantable Microstimulator” by Schulman et al. describes an implantable microstimulator used generally for stimulation of tissue. U.S. Pat. No. 6,037,704 titled “Ultrasonic Power Communication System” by Welle describes the use of ultrasound energy transfer from a transmitter to a receiver for purposes of powering a sensor or actuator without being connected by a lead/wire. U.S. Pat. No. 6,366,816 titled “Electronic Stimulation Equipment with Wireless Satellite Units” by Marchesi describes a tissue stimulation system based on a wireless radio transmission requiring the charging of a battery at the receiver and separate command signals used to control the delivery of stimulation. German patent application DE4330680A1 titled “Device for Electrical Stimulation of Cells within a Living Human or Animal” by Zwicker describes a general approach to power transfer using acoustic energy for tissue stimulation. U.S. Pat. No. 7,010,351 titled “Methods and apparatus for effectuating a lasting change in a neural-function of a patient” by Firlik et al. describes a DBS system used to treat or effectuate changes to neural function particularly by stimulation in the region of the cortex. U.S. Pat. No. 6,427,086 titled “Means and method for the intracranial placement of a neurostimulator” by Fischell et al. describes a DBS device implanted in the skull. U.S. Pat. No. 6,016,449 titled “System for treatment of neurological disorders” by Fischell et al. describes the use of a DBS device for the treatment of epilepsy. U.S. Pat. No. 5,782,798 titled “Techniques for treating eating disorders by brain stimulation and drug infusion” by Rise describes a DBS system for treating eating disorders with electrical stimulation in regions of the brain.
There are known attempts to use ultrasound for leadless stimulation but the efficiency of acoustic delivery of energy to the electrodes appeared to be very low. FIG. 2 illustrates an idea of DBS proposed in the U.S. Pat. No. 7,894,904 by Cowan et al. (incorporated herein by reference in its entirety), where a brain stimulation capability is achieved without the use of leads connected to a stimulation controller/pulse generator. Plane unfocused acoustic waves are used to deliver acoustic energy from the implanted in the skull controller-transmitter device 50 to the actual stimulator 70 implanted in the target area in the brain. An external controller 60 is used to communicate with the internal controller 50 via RF signal transmission for making adjustments to its operation. The proposed system of ultrasonic leadless delivery of energy to the stimulator may provide the complete control of the electrical pulse parameters; that is, the pulse amplitude, pulse duration, frequency, and the number of pulses. However, estimates show that only a tiny fraction, less than 0.1%, of acoustic energy is delivered to the stimulator. In such arrangement it is difficult to deliver sufficient levels of acoustic energy to the stimulator without negatively affecting (overheating) surrounding tissues.
Poor energy efficiency of currently known systems is a major obstacle to broad use of leadless implantable device. The need exists therefore for a system capable of delivering sufficient energy to the implantable stimulator without excessive heating of surrounding tissues.
Better focusing of ultrasound on the location of the stimulator may help to solve this problem. Focusing of ultrasonic waves is a fundamental feature of most medical applications of ultrasound. The efficiency of conventional methods of ultrasound focusing is often limited in biological tissues by spatial heterogeneities in sound velocity and by reflective surfaces and boundaries. This challenge is especially great for focusing through the skull bone, which induces severe refractions and scattering of the ultrasonic beam. There are many methods of improving ultrasonic focusing in complex media based on phase and amplitude corrections in the focusing system, but they are often complicated, and, in some cases, do not provide the necessary improvement.
An effective method for focusing in heterogeneous medium is a concept of Time-Reversed Acoustics (TRA), which provides an elegant possibility of both temporal and spatial concentrating of acoustic energy. It was initially developed by M. Fink of the University of Paris. The TRA technique is based on the reciprocity of acoustic propagation, which implies that the time-reversed version of an incident pressure field naturally refocuses on its source. The general concept of TRA is described in a seminal article by Fink, entitled “Time-reversed acoustics,” Scientific American, November 1999, pp. 91-97, which is incorporated herein by reference. U.S. Pat. No. 5,092,336 to Fink, which is also incorporated herein by reference, describes a device for localization and focusing of acoustic waves in tissues.
An important issue in the TRA method of focusing acoustic energy is related to obtaining initial signal from the target area. It is necessary to have a beacon located at the desired tissue location to record and provide an initial signal from the focal region. In the TRA systems described in the prior art, most commonly used beacon is a hydrophone placed at the chosen target point. Other disclosed beacons may include highly reflective targets that provide an acoustical feedback signal for TRA focusing of acoustic beam. The need to have a beacon in the target region limits the applications of TRA focusing methods.
While scattering and numerous reflections from boundaries are known to greatly limit and even completely diminish conventional ultrasound focusing, in TRA they lead to the improvement of the focusing results. Fink et al. have demonstrated a remarkable robustness of TRA focusing: the more complex the medium, the sharper the focus.
There is a need therefore for a leadless deep brain stimulation system configured for focused energy transmission to a specific site of the stimulator placement.